The long-term objective of the proposed research is to learn more about: 1) the effects of anesthetic agents on cerebral blood flow (CBF) and metabolism (CMR); 2) the relationships of these effects to basic pathomechanisms of focal ischemia; and 3) ways of modifying outcome from such ischemia insults occurring during anesthesia and surgery. Our specific aims are to test the hypotheses that: 1) the extent of permanent injury resulting from focal ischemia is related to the anesthetic present during the insult; 2) acute anesthetic- induced changes in CBF and CMR can be related to outcome: 3) the volume of brain tissue at risk for infarction is related to the manner in which different anesthetics preserve or alter the matching of CBF and CMR; 4) anesthetic effects on CBF and CMR relationships vary with time; and 5) the duration of anesthetic exposure prior to the ischemic insult will influence the volume of tissue "at risk" and this may vary with anesthetic agent. The following methodology will be used to test our hypotheses. Physiologically stable rats will be anesthetized with specific doses of isoflurane, halothane, or pentobarbital with duration of anesthetic exposure carefully controlled. Anesthetic effects on regional CBF and CMR will be simultaneously quantitated by 14C- iodoantipyrine and 14C-deoxglucose autoradiography respectively. Volume of ischemic tissue at risk for infarction as a result of middle cerebral artery occlusion will be determined by computer- assisted image analysis. This volume will then be related to anesthetic dose/response effects on CBF/CMR ratios. Outcome will be evaluated by: 1) computed quantitative 3-dimensional reconstruction of infarct volumes; 2) behavioral patterns; and 3) densitometric determination of brain water content. The health relatedness of this proposal derives from the fact that numerous conditions requiring surgery predispose patients to potentially disastrous cerebral ischemic insults while receiving anesthesia (e.g. carotid endarterectomy, cardiopulmonary bypass). Significant advances have been made in understanding basic pathomechanisms of cerebral ischemia and anesthetic effects on cerebral physiology, yet indications for application or avoidance of various anesthetic techniques during potentially ischemic clinical situations remain poorly defined. The proposed studies will contribute to our understanding of these problems.